Culturing hypoxia-primed mesenchymal stem cells in xeno- and serum-free conditions facilitates the synthesis of an extracellular matrix-based biologic with augmented therapeutic potential for the treatment of diabetic wounds

Sep 30, 2026

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Diabetic wound healing is severely impaired by poor angiogenesis, neuropathy, chronic inflammation, decreased cell proliferation, and dysregulated extracellular matrix (ECM) synthesis. A human mesenchymal stem cell (MSC)-derived ECM biologic was engineered to treat diabetic wounds using xeno- and serum-free components. Hypoxia-primed MSCs in a chemically defined medium produced a pro-angiogenic secretome. Aggregation with dextran sulfate created an ECM-DxS composite (MIPSOS) that enhanced pro-angiogenic bioactivity, accelerated revascularization and closure, improved infiltration and granulation, and reduced macrophage presence compared with GraftJacket®.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Keywords

Introduction

Impaired re-vascularization in diabetic wounds

Limitations of existing pro-angiogenic therapies

MSC and ECM-based alternatives

Lit etal. Stem Cell Research & Therapy (2026) 17:15 [https://doi.org/10.1186/s13287-025-04827-z](https://doi.org/10.1186/s13287-025-04827-z) Stem Cell Research & Therapy RESEARCH Open Access Culturing hypoxia-primed mesenchymal stem cells in xeno-and serum-free conditions facilitates the synthesis of an extracellular matrix-based biologic with augmented therapeutic potential for the treatment of diabetic wounds Kwok Keung Lit 1,2,3, Cheuk Kwan Owen Li 1,2, Zhamilya Zhirenova 1,2,3 and Anna Blocki 1,2,3,4* Abstract Diabetic wound healing is severely impaired by poor angiogenesis, neuropathy, chronic inflammation, decreased cell proliferation and dysregulated extracellular matrix (ECM) synthesis. Here, we developed a human mesenchymal stem cell (MSC)-derived ECM-based biologic with augmented pro-angiogenic potential, free of any xeno-and serum-free components, aimed at treating diabetic wounds. Hypoxia-primed MSCs, cultured in chemically defined medium, synthesized a secretome enriched in pro-angiogenic factors. This secretome was aggregated and coprecipitated by a heparan sulfate mimetic, dextran sulfate (DxS), into the pericellular space. MSCs assembled the deposited secretome components into an insoluble ECM, which upon decellularization was processed into MIcroParticles of SOlidified Secretome (MIPSOS), an ECM-DxS composite biologic. This formulation of MIPSOS demonstrated augmented pro-angiogenic bioactivity in vitro and in vivo and accelerated revascularization, reepithelization and wound closure by almost doubling wound closure rate, and outperforming GraftJacket®, a clinically utilized decellularized human dermis-derived biologic. MIPSOS-treated wounds showed enhanced cellular infiltration and granulation tissue formation, along with a reduced presence of macrophages, indicating progression toward inflammation resolution. MIPSOS thus provides a novel treatment alternative that overcomes major limitations of soluble factor-based, tissue-derived ECM-based, as well as cell-based therapies, offering significant improvements in diabetic wound management. Keywords Xeno-free/serum-free, Hypoxic culture, Extracellular matrix, Revascularization, Diabetic wound healing *Correspondence: Anna Blocki [anna.blocki@cuhk.edu.hk](anna.blocki@cuhk.edu.hk) 1Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China 2School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China 3Center for Neuromusculoskeletal Restorative Medicine (CNRM), Hong Kong Science Park, New Territories, Shatin, Hong Kong SAR, China 4Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. Lit et al. Stem Cell Research & Therapy (2026) 17:15 Introduction Impaired re-vascularization is one of the key pathophysiological features of chronic diabetic wound healing [1]. Due to the resulting poor tissue perfusion, ischemic tissues are continuously injured by low oxygen tension and

FAQs

How does hypoxia priming change MSC behavior for diabetic wound treatment?

Hypoxia-primed MSCs cultured in a chemically defined medium produce a secretome enriched with pro-angiogenic factors, which is then formulated into the therapeutic biologic.

What is MIPSOS, and how is it assembled?

MIPSOS is an ECM-DxS composite biologic created by aggregating/coprecipitating the MSC secretome with dextran sulfate (DxS), assembling deposited components into insoluble ECM, and then processing after decellularization into micro-particles of solidified secretome.

How does MIPSOS perform compared with a clinically used ECM-based product?

MIPSOS-treated wounds showed almost doubled wound closure rates and improved revascularization, re-epithelization, infiltration, and granulation, outperforming GraftJacket® while reducing macrophage presence.

Sep 30, 2026

Uploaded by Aldword